Tuberous sclerosis complex (TSC) is an autosomal-dominant hereditary disease characterized by hamartomas of multiple organ systems, including the brain, skin, heart, kidney and lung. Genetically, TSC is caused by pathogenic variants in the TSC1 or TSC2 gene. We reported a sporadic case of a 32-year-old Han Chinese male diagnosed with TSC, whose spouse had a history of two spontaneous miscarriages and an induced abortion of a 30-week fetus identified with cardiac rhabdomyoma by ultrasound. A novel heterozygous missense variant in the TSC2 gene (Exon35:c.4511 T > C:p.L1504P) was identified in the male patient and the aborted fetus by next-generation sequencing, but not in his wife or both his parents. According to the ACMG/AMP criteria, this variant was classified as a “likely pathogenic” variant. The novel TSC2:c.4511 T > C variant identified was highly likely associated with TSC and could potentially lead to adverse reproductive outcomes. IVF-ET and pre-implantation genetic diagnosis for TSC are recommended for this patient in the future to prevent fetal TSC.

中文翻译：

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与结节性硬化症相关的新型TSC2 c.4511 T> C错义变异体。

结节性硬化症（TSC）是常染色体显性遗传性疾病，其特征是多种器官系统的错构瘤，包括脑，皮肤，心脏，肾脏和肺。从遗传学上讲，TSC是由TSC1或TSC2基因中的致病性变异引起的。我们报告了一个零星病例，其中一名32岁的汉族男性被确诊为TSC，其配偶有两次自然流产史，并通过超声被鉴定出患有心型横纹肌瘤的30周胎儿流产。通过下一代测序，在男性患者和流产胎儿中发现了TSC2基因的新型杂合错义变体（Exon35：c.4511 T> C：p.L1504P），但在其妻子或父母双方中均未发现。根据ACMG / AMP标准，此变体被分类为“可能致病”变体。新颖的TSC2：c.4511 T> 确定的C变异体很可能与TSC相关，并可能导致不良的生殖结果。将来建议该患者进行IVF-ET和TSC的植入前遗传学诊断，以预防胎儿TSC。